New Zealand Datasheet Name of Medicine …

1 1 CATAPRES NZ DS v01 New Zealand Datasheet 1. PRODUCT name CATAPRES 150 mcg tablets CATAPRES 150 mcg/mL solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION CATAPRES 150 mcg tablets One tablet contains 150 mcg clonidine hydrochloride Excipient with known effect: One tablet contains mg lactose monohydrate CATAPRES 150 mcg/mL solution for injection Each 1 mL ampoule contains 150 mcg clonidine hydrochloride For full list of excipients, see section 3. PHARMACEUTICAL FORM CATAPRES 150 mcg tablets 150 mcg scored white compressed, impressed with the symbol 15C/15C on one side and the company symbol on the other side CATAPRES 150 mcg/mL solution for injection 150 mcg/mL clear, colourless solution 4. CLINICAL PARTICULARS Therapeutic indications Oral CATAPRES is indicated in the treatment of hypertension.

2 CATAPRES may be employed alone or concomitantly with other antihypertensive agents. Parenteral For the treatment of hypertensive crises, slow parental administration is especially suitable due to the rapid onset of action. Dose and method of administration Tablets It is recommended to slowly titrate the oral dose of CATAPRES to satisfy the requirements of individual patients. Initially Commence on 75 mcg (half a tablet) at night. At successive consultations (2-4 week intervals) the daily dose should be increased by half a tablet (75 mcg), until adequate blood pressure control is attained. The total daily dose is recommended to be taken once daily at night if the optimal dose is 1 tablet or less. If the total daily dose is greater than 1 tablet then dosage should be taken twice daily in evenly divided doses.

3 Where the dosage is uneven the larger dose should be taken at night. Usually doses above 600 mcg per day do not result in a further marked drop in blood pressure. Maintenance Most patients with mild to moderate hypertension will be controlled on a dose of 150-450 mcg daily. 2 CATAPRES NZ DS v01 In more severe cases, higher doses of up to 900 mcg daily have been utilised on a 300 mcg (2 tablets), twice to three times daily dosage regimen. Injection CATAPRES ampoules when administered subcutaneously or intramuscularly should be given with the patient in a recumbent position. A dosage of mcg/kg/minute is recommended for infusion. The rate of infusion should not exceed mcg/kg/minute to avoid transient blood pressure increase. No more than should be used per infusion.

4 If necessary, ampoules can be administered parenterally up to four times a day. CATAPRES ampoules contain less than 1 mmol sodium (23 mg) per ampoule, essentially sodium-free . Renal insufficiency Dosage must be adjusted according to the individual antihypertensive response which can show high variability with renal insufficiency according to the degree of renal impairment. Careful monitoring is required. Since only a minimal amount of clonidine is removed during routine haemodialysis, there is no need to give supplemental clonidine following dialysis. Contraindications CATAPRES should not be used in patients with known hypersensitivity to the active ingredient or other components of the product, and in patients with severe bradyarrhythmia resulting from either sick sinus syndrome or AV blocks of 2nd or 3rd degree.

5 In case of rare hereditary conditions that may be incompatible with an excipient of the product (see section ) the use of the product is contraindicated. Special warnings and precautions for use CATAPRES should be used with caution in patients with mild to moderate bradyarrhythmia, such as low sinus rhythm, with disorders of cerebral or peripheral perfusion, depression, polyneuropathy and constipation. In hypertension caused by phaeochromocytoma no therapeutic effect of CATAPRES can be expected. Clonidine, the active ingredient of CATAPRES, and its metabolites are extensively excreted with the urine. Renal insufficiency requires particularly careful adjustment of dosage (see section ). As with other antihypertensive drugs, treatment with CATAPRES should be monitored particularly carefully in patients with heart failure or severe coronary disease.

6 In patients who have developed localised skin reaction to CATAPRES TTS transdermal patch, substitution of oral clonidine therapy may be associated with the development of a generalised rash. Patients should be instructed not to discontinue therapy without consulting their physician. Following sudden discontinuation of CATAPRES after prolonged treatment with high doses, restlessness, palpitations, rapid rise in blood pressure, nervousness, tremor, headaches or nausea 3 CATAPRES NZ DS v01 have been reported. When discontinuing therapy with CATAPRES, the physician should reduce the dose gradually over 2 - 4 days. An excessive rise in blood pressure following discontinuation of CATAPRES therapy can be reversed by intravenous phentolamine or tolazoline (see section ) If long-term treatment with a beta-blocker has to be interrupted, then the beta-blocker should first be phased out gradually, followed by the clonidine.

7 Patients who wear contact lenses should be warned that treatment with CATAPRES may cause decreased lacrimation. The use and the safety of clonidine in children and adolescents has little supporting evidence in randomised controlled trials and therefore can not be recommended for use in this population. In particular, when clonidine is used off-label concomitantly with methylphenidate in children with ADHS, serious adverse reactions, including death, have been observed. Therefore, clonidine in this combination is not recommended. CATAPRES tablets contain mg of lactose monohydrate per maximum recommended daily dose. Patients with the rare hereditary conditions of galactose intolerance galactosaemia should not take this Medicine . Interaction with other medicines and other forms of interaction The reduction in blood pressure induced by clonidine can be further potentiated by concurrent administration of other hypotensive agents.

8 This can be of therapeutic use in the case of other antihypertensive agents such as diuretics, vasodilators, beta-receptor blockers, calcium antagonists and ACE-inhibitors, but not alpha1-blocking agents. Substances which raise blood pressure or induce a Na+ and water retaining effect such as non steroidal anti inflammatory agents can reduce the therapeutic effect of clonidine. Substances with alpha2-receptor blocking properties such as phentolamine or tolazoline may abolish the alpha2-receptor mediated effects of clonidine in a dose dependant manner. Concomitant administration of substances with a negative chronotropic or dromotropic effect such as beta-receptor blockers or digitalis glycosides can cause or potentiate bradycardic rhythm disturbances.

9 It cannot be ruled out that concomitant administration of a beta-receptor blocker will cause or potentiate peripheral vascular disorders. Studies with combined administration of clonidine and beta-receptor blockers have shown that if treatment is to be discontinued, the dose of the beta-receptor blocker must always be slowly diminished first followed by the clonidine. The antihypertensive effect of clonidine may be reduced or abolished and orthostatic regulation disturbances may be provoked or aggravated, by concomitant administration of tricyclic anti-depressants or neuroleptics with alpha-receptor blocking properties. Based on observations in patients in a state of alcoholic delirium it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT-prolongation, ventricular fibrillation) of high intravenous doses of haloperidol.

10 Causal relationship and relevance for antihypertensive treatment have not been established. The effect of centrally depressant substances or alcohol can be potentiated by clonidine. 4 CATAPRES NZ DS v01 Fertility, pregnancy and lactation Pregnancy (Category B3) There are limited amount of data from the use of clonidine in pregnant women. During pregnancy, CATAPRES, as with any medication, should only be administered if the benefit justifies any possible risks to the foetus. Careful monitoring of mother and child is recommended. Clonidine passes the placental barrier and may lower the heart rate of the foetus. There is no adequate experience regarding the long-term effects or prenatal exposure. During pregnancy, the oral forms of clonidine should be preferred.